Juntendo University Graduate School of Medicine, Tomioka, Urayasu, Chiba, Japan.
Clin Exp Dermatol. 2013 Aug;38(6):665-8. doi: 10.1111/ced.12100. Epub 2013 Jun 8.
Epidermal hyperinnervation is considered one cause of sensitization to itch, and is thought to regulated by keratinocyte-derived axonal guidance molecules, including nerve growth factor (NGF) and semaphorin (Sema)3A. Neurotropin (NTP) shows antipruritic effects in allergic disease and is also used for pain relief. Using cultured rat dorsal root ganglion neurones, we previously found that NTP inhibited NGF-induced neurite outgrowth. However, no such inhibitory effect has been shown in vivo. We therefore assessed the effects of intraperitoneal administration of NTP on nerve density and expression of NGF and Sema3A mRNAs in the epidermis of acetone-treated mice showing epidermal hyperinnervation. We found that NTP significantly reduced intraepidermal nerve growth in these acetone-treated mice. NTP significantly upregulated epidermal Sema3A mRNA, but had no effect on expression of epidermal NGF mRNA. These findings indicate that NTP may reduce intraepidermal nerve density by inducing expression of Sema3A in the epidermis.
表皮神经支配过度被认为是瘙痒致敏的一个原因，其被认为受到角质形成细胞衍生的轴突导向分子的调节，包括神经生长因子（NGF）和 Sema3A。神经生长调节蛋白（NTP）在过敏疾病中显示出止痒作用，也用于缓解疼痛。使用培养的大鼠背根神经节神经元，我们之前发现 NTP 抑制 NGF 诱导的轴突生长。然而，在体内没有显示出这种抑制作用。因此，我们评估了腹腔内给予 NTP 对丙酮处理的小鼠表皮中神经密度和 NGF 和 Sema3A mRNA 表达的影响，这些小鼠表现出表皮神经支配过度。我们发现 NTP 显著减少了这些丙酮处理小鼠的表皮内神经生长。NTP 显著上调表皮 Sema3A mRNA，但对表皮 NGF mRNA 的表达没有影响。这些发现表明 NTP 可能通过诱导表皮中 Sema3A 的表达来减少表皮内神经密度。
